Quantitative analysis of near-implant magnesium accumulation for a Si-containing coated AZ31 cage from a goat cervical spine fusion model

Abstract

BackgroundMagnesium (Mg) released from Mg-based implants degradation is believed to be effective in improving osteogenesis, however, studies focusing on Mg-based interbody cages are limited and fusion success was never reported. As excessive Mg accumulation can inhibit new bone formation, this study is designed to explain the possible reasons for the fusion failure of Mg-based cages by analyzing the relationships between the intervertebral Mg accumulation and the resulting interbody fusion.MethodsThe experimental cage was consisted of magnesium alloy (AZ31) substrate and Silicon (Si) -containing coating. C3/C4 and C5/C6 of 24 goats were implanted with cage or autologous iliac crest bone graft (Control group), which were analyzed at 3, 6, 12, and 24 weeks post-operatively. Intervertebral Mg concentrations, Mg-related Calcium (Ca)/ Phosphorus (P) ratios, radiological evaluations and histological findings were recorded for analyzing the relationships between the three of cage corrosion, Mg accumulation, and interbody fusion.ResultsIntervertebral Mg levels were significantly increased after cage implantation, especially in the areas that were closer to the cages at 3 weeks post-operatively, and these increased concentrations could persist up to 12 weeks post-operatively, indicating a relatively rapid corrosion process. Significantly lower Mg levels were only found at 24 weeks post-operatively, but these levels were still higher than those of the control group. In addition, Mg was found to be widely distributed at the intervertebral space since high Mg concentrations could even be detected at the posterior boundary of the vertebral body. Under this Mg accumulation profile, interbody fusion was not achieved, as indicated by the decreased Ca/P ratios, low CT fusion scores and negative histological results.ConclusionsIntervertebral excessive Mg accumulation might be the primary reason for interbody fusion failure. Quantitative Mg analysis can offer insight into the association between cage degeneration and biological response.

Bioabsorbable high-purity magnesium interbody cage: degradation, interbody fusion, and biocompatibility from a goat cervical spine model

“…The blood supply to the postoperative interbody space and mechanical environment are different from those in the long bone after ACDF, which may attribute to the different degradation rates of Mg-based materials at distinct anatomic structures, leading to the therapeutic failure. Our results showed the degradation rate was relatively fast within 3 weeks and thereafter remained stable, which was consistent with previously reported (12,13,17). Moreover, the 300-400 μm space around the HP Mg cage was filled with proliferative fibrous tissues, which may be ascribed to the early intrinsic response to the foreign body.…”

“…According to our previous findings, the size of experimental cage was modified with the specification of 12 mm × 10 mm × 4-5 mm and a 7-degree wedge angle (Figure 1) (12,13). The cage was tested in a universal testing machine, the modulus of elasticity in compression was 609.43±52.16 MPa, the yield strength was 151.59±8.34 MPa and the compressive strength was 392.62±16.…”

“…This may be explained as that Mg 2+ released from Mgbased implants plays a significant and positive role in the osteogenic differentiation mediated by neuronal calcitonin gene-related polypeptide (CGRP) (7). In available studies, the application of Mg-based materials as a fusion cage fails in goat models (11)(12)(13). In the present study, our results for the first time indicated that Mg cage successfully induced intervertebral fusion which was confirmed histologically by the presence of bony junctions through the middle hole of the fusion cage between the upper and lower vertebral bodies at 24 weeks.…”

“…However, in the ACDF model of goat cervical vertebrae bearing force, although the development of Mg alloys composition and the addition of surface coating methods to improve the degradation of Mg-based cage, such as an AZ31 cage with poly-ε-caprolactone (PCL) coating, porous Mg-Zinc (Zn) alloy cage with a microarc oxidation (MAO)/silicon-(Si-) containing coating and AZ31 cage with Si-containing coating, the whole degradation rate was nonlinear in the 24-week observation period, the early degradation rate was relatively fast, which resulted in the formation of local Mg ion concentration in tissues. Thus, the bone healing is still poor after implantation of Mg-based cage, and fusion success has never been reported (11)(12)(13). The main barrier that limits the clinical application of Mgbased cages is adverse reactions secondary to their fast degradation which may be caused by intervertebral pressure and blood supply different from unforced bones (14).…”

Biomaterials for Interbody Fusion in Bone Tissue Engineering

“…The pore size of human cancellous bone is 500–600 μm ( Lim et al, 2019 ). Considering porous scaffolds applied in bone tissue engineering, the porosity should be >50%, especially in the range of 65–80%, where the structure and elasticity modulus are similar to those of human trabeculae ( Zhang F et al, 2018 ; Bai H. T. et al, 2020 ). The stress between the cage and the endplates decreases with increasing porosity, while the range of motion of the vertebral bodies decreases with increasing fusion rates of the upper and lower vertebral bodies.…”